Second Malignant Neoplasms in Childhood Cancer Survivors Treated in a Tertiary Paediatric Oncology Centre

: One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore.: A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed.: We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years (<0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies.: This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Osteogenic sarcoma in children and young adults

<p><b>INTRODUCTION</b>More than 80% of children with osteogenic sarcoma (OS) relapse and 35% to 40% of them die within the first 2 years after diagnosis due to relapse. We investigated the incidence, treatment modalities used and the outcome of patients with OS treated in Singapore.</p><p><b>MATERIALS AND METHODS</b>Patients with OS treated in Department of Paediatrics KK Women's and Children's Hospital (KKH) and National University Hospital (NUH) between January 1994 and June 2011 were reviewed. Chemotherapy was as per the European Osteosarcoma Intergroup (EOI) and as per the Memorial Sloan-Kettering Cancer Centre's (MSKCC) T12 protocols. Overall and event-free (EFS) 5-year survivals were calculated using Kaplan-Meier analysis and Cox proportional hazards regression analysis.</p><p><b>RESULTS</b>Of 66 patients with OS, 19 (29%) of them presented with metastatic OS. The median age of diagnosis was 12.1 years with 5-year overall survival of 61.7% (95% CI, 48.1 to 75.3). The 5-year overall survival for those with non-metastatic and metastatic OS was 73.1% (95% CI, 58.1 to 88.1) and 34.7% (95% CI, 8.7 to 60.7, P=0.007) respectively. The 5-year overall survival for those treated as per the MSKCC T12 and EOI was 72.4% (95% CI, 52.6 to 92.2) and 54.3% (95% CI, 36.3 to 72.3, P=0.087) respectively. After controlling for confounding factors, patients with non-metastatic OS had higher 5-year EFS (HR, 0.228, 95% CI, 0.096 to 0.541, P=0.001) and overall survival (HR, 0.294, 95% CI, 0.121 to 0.713, P=0.007) compared to those with metastatic OS. Non-metastatic OS patients treated as per EOI regimen had lower 5-year EFS (HR, 2.397, 95% CI, 1.012 to 6.678, P=0.047) compared to those treated per MSKCC T12 regimen.</p><p><b>CONCLUSION</b>Multidrug combination chemotherapy including high-dose methotrexate (HD-MTX) and a multidisciplinary team approach introduced in 2003 in Singapore is well tolerated and can be safely delivered. The survival benefit between the 2 regimens still needs to be explored.</p>

Singapore rhabdomyosarcoma (RMS) experience: shall we change our practice?

<p><b>INTRODUCTION</b>Although rhabdomyosarcoma (RMS) constitutes nearly 4% of all children diagnosed with cancer in the ethnically diverse small island city of Singapore, it is unknown how children with RMS fare.</p><p><b>MATERIALS AND METHODS</b>This study investigated 50 children with RMS from April 1993 to December 2010 from KK Women's and Children's Hospital (KKH) and National University Hospital (NUH). They were treated either as per Intergroup Rhabdomyosarcoma Study Group (IRSG) or Société Internationale Pediatrique D'Oncologie (SIOP) regimens.</p><p><b>RESULTS</b>Median age of diagnosis was 5.1 years (range, 0.1 to 17.3 years) with a median follow-up of 3.3 years (range, 0.4 to 15.6 years). According to IRSG classifi cation, 18 (36%) were staged as low-risk (LR); 19 (38%) were intermediate-risk (IR), 12 (24%) were high-risk (HR) and it was unknown in 1 patient. Twenty-nine (58%) were of embryonal subtype, 17 (34%) were alveolar and subclassification was not available in 4. The primary sites of tumour were: head and neck region (n = 22); genitourinary (n = 19); extremity (n = 10); and abdomen/retroperitoneal (n = 5). At the time of analysis, 80% were alive with no evidence of disease, 9 were dead of disease, and 2 were alive with disease. By disease risk group, the 5-year event-free survival (EFS) for LR group disease was 81.3% (95% CI, 62.0 to 100.0), IR group was 61.4% (95% CI, 32.3 to 90.4) and HR group was 25.0% (95% CI, 0.0 to 49.5) respectively (P <0.001). The 5-year EFS for risk by chemotherapy received as per SIOP vs per IRSG revealed: LR 83.3% vs 75.0% (P = 0.787); IR 83.3% vs 43.8% (P = 0.351); HR 0.0% vs 42.9% (P = 0.336) respectively. Of 15 relapses (HR, n = 7), at median of 2 years, 4 of 6 patients treated as per SIOP regimen were dead of disease and 3 of 8 treated as per IRSG were alive.</p><p><b>CONCLUSION</b>Radiation therapy (RT) can be avoided in LR classification although those in higher risk classification need RT to local and distant metastatic disease. The outcome of children with RMS in Singapore can be further improved by coming together as a cooperative group to provide the best total care. Improved communication, multidisciplinary team collaboration, standardisation of protocols and rigorous data collection are keys.</p>

The hidden impact of childhood cancer on the family: a multi-institutional study from Singapore

<p><b>INTRODUCTION</b>The care of children with cancer creates emotional and financial hardships for their families. There is a lack of information on the impact of childhood cancer on the family as a whole in Singapore. Thus, we set out to assess the financial impact as well as its psychosocial impact in our local context.</p><p><b>MATERIALS AND METHODS</b>All patients diagnosed and treated for cancer at the Departments of Paediatrics, KK Women's and Children's Hospital and National University Hospital, Singapore were eligible for this study. Families of these patients completed 2 self-administered questionnaires: (i) About-you and your-family and (ii) the Impact-On-Family scale. For the latter, the total score was obtained by the summation of all scores, where high scores correlated to high impact.</p><p><b>RESULTS</b>Seventy-nine parents were enrolled during the study period from October 2008 to February 2009. Being of Malay/Indian origin was associated with a high overall family burden. On the other hand, being of Malay/Indian origin was also associated with most successful at mastery when a child was diagnosed with cancer (P = 0.001). In addition, when compared to caregivers who remained employed, those who were asked to quit their job, experienced a higher Financial Burden (P = 0.03), a high Familial/Social Burden (P = 0.05) and a high Personal Strain (P = 0.03).</p><p><b>CONCLUSION</b>Childhood cancer impacted family life in Singapore at many levels. In particular, the factors involved are various cultural discourses; employment status of caregivers; and those whose leave/pay are affected.</p>

Health-related quality of life in children with cancer undergoing treatment: a first look at the Singapore experience

<p><b>INTRODUCTION</b>With intensive chemotherapy and increased survival, quality of life in our paediatric population is of increasing concern. The aim of this study was to assess the children's quality of life during the treatment process.</p><p><b>MATERIALS AND METHODS</b>Patients between the ages of 7 and 18 years old who are undergoing cancer treatment in the Division of Paediatric Haematology-Oncology, Department of Paediatrics, National University Health System, were identified. The child self-reported his/her health-related quality of life (HRQOL) using the PedsQL Paediatric Quality of Life Inventory and Cancer module as a validated assessment tool.</p><p><b>RESULTS</b>Thirty-two patients were enrolled over a 3-week period in November 2007. The median age was 11 years (range, 7 to 17). There was 1 non-responder (3%). Fourteen (45%) boys and 17 (55%) girls were interviewed. There were 8 (26%) and 23 (74%) patients with solid and haematologic malignancies, respectively. For the Cognitive Problem Dimension score, 86% of patients with haematologic malignancy and 50% of those with solid malignancy scored below the 75th percentile (82), [OR 0.72 (0.01-0.8), P = 0.03]. For the Physical Health Summary score, patients with solid malignancy scored worse, 25% below the 10th percentile, as compared to 4.3% of patients with haematologic malignancy. This is reflected by a worse Pain and Hurt Dimension score for patients with solid malignancy. For the Perceived Appearance Dimension score, patients with solid malignancy (75%) scored lower than the median score (67) compared to those with haematologic malignancy (44%).</p><p><b>CONCLUSIONS</b>The domains of HRQOL are affected to different extents for the patients with solid and those with haematologic malignancy. This is most likely to be due to the differences in treatment strategies and clinical course. Healthcare professionals should be aware of the effects of treatment on HRQOL and take practical steps to address these issues.</p>

A report from the Singapore Childhood Cancer Survivor Study (SG-CCSS): a multi-institutional collaborative study on long-term survivors of childhood cancer, initial analysis reporting for the SG-CCSS

<p><b>INTRODUCTION</b>Worldwide, the survival rates among childhood cancer patients are increasing. As such, assessing the risk of late effects and complications are increasingly becoming more important. The degree of risk of late effects may be influenced by various treatment-related factors.</p><p><b>MATERIALS AND METHODS</b>The Singapore Childhood Cancer Survivor Study (SGCCSS) consists of all individuals who survived at least 2 or more years after treatment for cancer diagnosed during childhood or adolescence. Phase I of SG-CCSS is the identification of all eligible patients between 1981 and 2005.</p><p><b>RESULTS</b>There were a total of 1440 patients registered in the Singapore Childhood Cancer Registry. Among these, 704 (48.9%) patients were from the KK Women's and Children's Hospital (KKH) and 626 (43.5%) were from the National University Hospital (NUH). Of all the registered patients, the most common cancer in childhood was leukaemia [42.6% (n = 613)] and the second most common was brain tumour [14.9% (n = 215)]. A total of 1043 (72.4%) patients were surviving, of whom 839 (80.4%) were long-term survivors. Haematological malignancies were found in 492 (58.6%) survivors whilst 347 (41.4%) were diagnosed with various solid tumours. Among leukaemic patients (n = 613), 65.6% (n = 402) were long-term survivors. Acute lymphoblastic leukaemia (ALL) (n = 484) had the highest percentage of [80.9% (n = 392)] of surviving patients, of whom 73.4% were long term-survivors. For brain tumour (n = 215), there were 95 (44.2%) long-term survivors.</p><p><b>CONCLUSION</b>Preliminary analysis revealed that 58.3% of patients were long-term survivors. Our hope is to tailor all future therapy for childhood cancers, optimising cure rates whilst minimising long-term side-effects.</p>

Retinoblastoma: a recent experience at the National University Hospital, Singapore

<p><b>INTRODUCTION</b>Retinoblastoma is a very rare disease. There were 30 cases of retinoblastoma diagnosed and treated at National University Hospital (NUH).</p><p><b>MATERIALS AND METHODS</b>A retrospective chart review was performed on the medical records of 30 patients who were diagnosed with retinoblastoma between 1995 and 2008 at the Department of Paediatrics, National University Hospital, Singapore.</p><p><b>RESULTS</b>The median age at diagnosis was 1.6 years (range, 0-5.9) with a median follow-up of 1.8 years (range, 0.1 to 11.6). The median time from presenting signs to the time of diagnosis was 5.2 months (range, 0-25.2). Common presenting signs of retinoblastoma were identified; the most common of which were leukocoria (50.0%), squinting (13.3%), poor vision (10.0%), strabismus (6.6%) and unknown (33.3%). Of the 30 patients, 10 were from Singapore whilst the other 20 patients were from the surrounding countries. Twelve patients had bilateral disease at the time of diagnosis, while 18 had unilateral disease. Staging information was available in 27 patients. Enucleation was performed in 25 of 30 patients. Radiation therapy was given in 3 patients in 1995 (bilateral disease), 2001 (bilateral disease) and 2003 (unilateral disease). At the time of analysis, 19 patients were alive with no evidence of disease. Overall 5-year survival for the cohort was 88.1% [95% confidence interval (CI), 88.0-100] and event-free survival for the whole cohort was 74.2% (95% CI, 55.8-92.6).</p><p><b>CONCLUSION</b>In our limited experience, the importance of collaboration and standardisation of the staging system, raising awareness and education of primary healthcare providers and parents are strongly stressed.</p>